PT - JOURNAL ARTICLE AU - Elizabeth D. Ferucci AU - Erika Darrah AU - Irene Smolik AU - Tammy L. Choromanski AU - David B. Robinson AU - Marianna M. Newkirk AU - Marvin J. Fritzler AU - Antony Rosen AU - Hani S. El-Gabalawy TI - Prevalence of Anti-Peptidylarginine Deiminase Type 4 Antibodies in Rheumatoid Arthritis and Unaffected First-degree Relatives in Indigenous North American Populations AID - 10.3899/jrheum.130293 DP - 2013 Aug 01 TA - The Journal of Rheumatology PG - jrheum.130293 4099 - http://www.jrheum.org/content/early/2013/07/23/jrheum.130293.short 4100 - http://www.jrheum.org/content/early/2013/07/23/jrheum.130293.full AB - Objective To determine whether anti-peptidylarginine deiminase type 4 (PAD4) antibodies were present in first-degree relatives (FDR) of patients with rheumatoid arthritis (RA) in 2 indigenous North American populations with high prevalence of RA. Methods Participants were recruited from 2 indigenous populations in Canada and the United States, including patients with RA (probands), their unaffected FDR, and healthy unrelated controls. Sera were tested for the presence of anti-PAD4 antibodies, anticyclic citrullinated peptide (anti-CCP) antibodies, and rheumatoid factor (RF). HLA-DRB1 subtyping was performed and participants were classified according to number of shared-epitope alleles present. Results Antibodies to PAD4 were detected in 24 of 82 (29.3%) probands; 2 of 147 (1.4%) relatives; and no controls (p < 0.0001). Anti-CCP was present in 39/144 (27.1%) of the relatives, and there was no overlap between positivity for anti-CCP and PAD4 in the relatives. In RA patients, anti-PAD4 antibodies were associated with disease duration (p = 0.0082) and anti-CCP antibodies (p = 0.008), but not smoking or shared-epitope alleles. Conclusion Despite a significant prevalence of anti-CCP in FDR, anti-PAD4 antibodies were almost exclusively found in established RA. The prevalence of anti-PAD4 antibodies in RA is similar to the prevalence described in other populations and these autoantibodies are associated with disease duration and anti-CCP in RA.